Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria

Gastroenterology. 2005 Apr;128(4):891-906. doi: 10.1053/j.gastro.2005.02.009.


Background & aims: To explore the hypothesis that selective immune responses to distinct components of the intestinal microflora induce intestinal inflammation, we characterized disease kinetics and bacterial antigen-specific T-cell responses in ex germ-free interleukin 10 -/- and wild-type control mice monoassociated with Enterococcus faecalis , Escherichia coli , or Pseudomonas fluorescens .

Methods: Colitis was measured by using blinded histological scores and spontaneous interleukin 12 secretion from colonic strip culture supernatants. Interferon gamma secretion was measured from mesenteric or caudal lymph node CD4 + T cells stimulated with bacterial lysate-pulsed antigen-presenting cells. Luminal bacterial concentrations were measured by culture and quantitative polymerase chain reaction.

Results: Escherichia coli induced mild cecal inflammation after 3 weeks of monoassociation in interleukin 10 -/- mice. In contrast, Enterococcus faecalis-monoassociated interleukin 10 -/- mice developed distal colitis at 10-12 weeks that was progressively more severe and associated with duodenal inflammation and obstruction by 30 weeks. Neither bacterial strain induced inflammation in wild-type mice, and germ-free and Pseudomonas fluorescens-monoassociated interleukin 10 -/- mice remained disease free. CD4 + T cells from Enterococcus faecalis- or Escherichia coli-monoassociated interleukin 10 -/- mice selectively produced higher levels of interferon gamma and interleukin 4 when stimulated with antigen-presenting cells pulsed with the bacterial species that induced disease; these immune responses preceded the onset of histological inflammation in Enterococcus faecalis -monoassociated mice. Luminal bacterial concentrations did not explain regional differences in inflammation.

Conclusions: Different commensal bacterial species selectively initiate immune-mediated intestinal inflammation with distinctly different kinetics and anatomic distribution in the same host.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cecal Diseases / microbiology
  • Cecal Diseases / pathology
  • Chronic Disease
  • Colitis / microbiology
  • Colitis / pathology
  • Colony Count, Microbial
  • Cytokines / biosynthesis
  • Disease Progression
  • Enterococcus faecalis* / immunology
  • Enterocolitis / genetics*
  • Enterocolitis / metabolism
  • Enterocolitis / microbiology*
  • Enterocolitis / pathology
  • Escherichia coli / immunology
  • Escherichia coli Infections* / microbiology
  • Gastroenteritis / microbiology
  • Gastroenteritis / pathology
  • Gram-Positive Bacterial Infections* / microbiology
  • Interleukin-10 / deficiency*
  • Intestinal Mucosa / metabolism
  • Lymph Nodes / immunology
  • Mice
  • Mice, Knockout
  • Phenotype


  • Antigens, Bacterial
  • Cytokines
  • Interleukin-10